chr2-242793-G-C

Position:

• chr2-242793-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282687.2(SH3YL1):​c.3+5C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,533,988 control chromosomes in the GnomAD database, including 51,992 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4378 hom., cov: 33)
  • Exomes 𝑓: 0.26 (47614 hom.)
• Consequence: SH3YL1 NM_001282687.2 splice_region, intron
• Scores: Splicing: ADA: 0.00008660
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243

Genes affected

SH3YL1 (HGNC:29546): (SH3 and SYLF domain containing 1) Enables phosphatase binding activity and phosphatidylinositol binding activity. Predicted to act upstream of or within phosphatidylinositol biosynthetic process and regulation of ruffle assembly. Located in ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3YL1	NM_015677.4	c.291+4745C>G		intron_variant		ENST00000356150.10	NP_056492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3YL1	ENST00000356150.10	c.291+4745C>G		intron_variant		1	NM_015677.4	ENSP00000348471.5
SH3YL1	ENST00000626873.2	c.3+5C>G		splice_region_variant, intron_variant		5		ENSP00000485824.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35205 AN: 151884 Hom.: 4380 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.201

GnomAD3 exomes AF: 0.247 AC: 34148 AN: 138376 Hom.: 4524 AF XY: 0.251 AC XY: 18562 AN XY: 73986

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.198

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.218

Gnomad SAS exome AF: 0.278

Gnomad FIN exome AF: 0.328

Gnomad NFE exome AF: 0.255

Gnomad OTH exome AF: 0.235

GnomAD4 exome AF: 0.259 AC: 357661 AN: 1381986 Hom.: 47614 Cov.: 37 AF XY: 0.260 AC XY: 177288 AN XY: 681612

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.199

Gnomad4 ASJ exome AF: 0.225

Gnomad4 EAS exome AF: 0.206

Gnomad4 SAS exome AF: 0.287

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.232 AC: 35205 AN: 152002 Hom.: 4378 Cov.: 33 AF XY: 0.235 AC XY: 17469 AN XY: 74300

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.199

Alfa AF: 0.219 Hom.: 1319

Bravo AF: 0.215

Asia WGS AF: 0.255 AC: 891 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000087
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs62114506; hg19: chr2-242793; COSMIC: COSV62156457;